Acute coronary syndrome by HC120606095948

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									2008 Clinical Trial
 Summary Slides



ACC Annual Scientific Session
  AHA Scientific Sessions
      ESC Congress
 ACC.08/SCAI-ACCi2

Clinical Trial Summary Slides
                                ACCOMPLISH
Trial design: Patients with hypertension were randomized to fixed dose
amlodipine/benazapril or hydrochlorothiazide (HCTZ)/benazapril. Patients were followed for
3 years.

                                                 Results
              (p = 0.0002)                       • Systolic blood pressure ↓ by amlodipine/benazapril,
                                                   compared with HCTZ/benazapril by 0.7 mm Hg (p <
                                                   0.05)
               11.4     9.2                      • Primary endpoint : CV mortality, stroke, MI,
                                                   revascularization, unstable angina, resuscitation from
    12
                                                   death 9.2% in amlodipine/benazapril arm, compared
                                                   with 11.4% in HCTZ/benazapril arm (p = 0.0002)
    8
%
    4                                            Conclusions
                                                 • Fixed dose combination of amlodipine/benazapril is
                                                   better than HCTZ/benazapril in reduction in blood
    0
                                                   pressure as well as cardiovascular endpoints in
             Primary endpoint                      patients with high-risk hypertension
  HCTZ/benazapril        Amlodipine/benazapril
    (n = 5,721)               (n = 5,741)


                                                  Presented by Dr. Kenneth Jamerson at SCAI-ACC i2
                                                  Summit/ACC 2008
Adjusted Clopidogrel Loading Doses According to VASP Phosphorylation
Index Decrease Rate of Major Adverse Cardiovascular Events in Patients
                      With Clopidogrel Resistance
     Trial design: Patients with clopidogrel resistance (VASP index >50%) randomized to
     VASP-guided extra clopidogrel dosing (n = 78) or PCI without add’l clopidogrel (n = 84).


                                                                Results
                                                                • 86% of VASP-guided patients overcame
             (p = 0.007)            (p = 1.0)                     resistance with 1-3 extra clopidogrel doses
                                                                • MACE: 0% for VASP-guided vs. 9.5% for
                                                                  control (p =0.007)
    12
            0             9.5
                                                                • Total bleeding: 3.9% vs. 4.8%, respectively (p
     8                                                            = 1.0)
%                                  3.9                    4.8
     4
     0           M A CE                  T ot al bl eedi ng



                MACE            Total bleeding                  Conclusions
                                                                • Clopidogrel resistance was reversed with
                VASP-guided            No extra
                    extra            clopidogrel
                                                                  VASP-guided additional clopidogrel dosing
                 clopidogrel           (n = 84)                 • Effective response to clopidogrel resulted in
                   (n = 78)
                                                                  less MACE and similar bleeding



                                                                Bonello L, et al. J Am Coll Cardiol 2008;51: [Published
                                                                online 29 March 2008]
                                                      A-F
    Trial design: NSTEMI patients were randomized to PCI plus FilterWire EZ embolic
    protection (n = 77) or standard PCI without embolic protection (n = 74).


                                                        Results
               (p = ns)            (p = ns)             • In-hospital MACE: 11.7% with FilterWire vs.
                                                          9.5% with standard PCI (p = ns)
                                 94        94
    100                                                 • 30-day MACE: 12% vs. 11% (p = ns),
                                                          respectively
                                                        • TIMI 3 flow post-PCI: 94% vs. 94% (p = ns),
%    50
                                                          respectively
             11.7    9.5
      0
            In-hospital MACE   TIMI 3 flow post-PCI
                                                        Conclusions
            In-hospital          TIMI 3 flow
                                                        • FilterWire EZ embolic protection is not
              MACE                post-PCI
                                                          beneficial in NSTEMI
                                                        • PCI plus FilterWire results in similar in-hospital
                                                          MACE, 30-day MACE, and TIMI 3 flow post-
             PCI plus           Standard PCI              PCI compared with standard PCI
             embolic
            protection


                                                            Presented by Dr. Mark Webster at SCAI-ACC i2
                                                            Summit/ACC 2008
                                                      ALLAY
   Trial design: Overweight hypertensive patients with evidence of left ventricular (LV)
   hypertrophy were randomized to aliskiren, losartan, or the combination. Patients were
   followed for 36 weeks to assess the change in LV mass index on cardiac MRI.

                                                              Results
                            (p < 0.0001*)                     • Change in LV mass index 4.9 ± 1, 4.8 ± 1, and 5.8 ±
                               (p = 0.52**)                     0.9 with aliskiren, losartan, and combination,
                                                                respectively (all p < 0.0001 compared with baseline)
                         4.9        4.8       5.8             • Aliskiren was noninferior to losartan (p < 0.0001), but
               6
                                                                combination not superior to losartan alone (p = 0.52)
                                                              • Incidence of serious side effects was similar (p = 0.77)
               4
        g/m2




                                                              Conclusions
               2                                              • Aliskiren was noninferior to losartan in reducing LV
                                                                mass index, but the combination was not superior
               0                                                to losartan alone

                     Primary endpoint                         • Clinical outcomes studies are awaited

      Aliskiren             Losartan            Combination
      (n = 154)             (n = 152)            (n = 154)
* Aliskiren vs. losartan for noninferiority
                                                                Presented by Dr. Scott Solomon at SCAI-ACC i2
** Combination vs. losartan                                     Summit/ACC 2008
                                 ARMYDA-RELOAD
       Trial design: Patients on chronic clopidogrel therapy (>10 days) undergoing PCI were
       randomized to an additional 600 mg clopidogrel dose (n = 285) or placebo (n = 283) and
       followed for 30 days.

                                                     Results
               (p = 0.70)           (p = 0.035)
                                                     • Approximately one-third had unstable angina
                                                     • MACE in entire study: 7% in reload group vs.
                                     7     18
  20                                                   9% in placebo group (p = 0.70)
                                                     • MACE in ACS patients: 7% vs. 18%
              7         9
                                                       respectively, (p = 0.035)
% 10                                                 • No major bleeds in either group


   0                                                 Conclusions
            MACE
           MACEentire study
                 in entire       MACE ACS patients
                                 MACE in ACS         • Among unselected patients on chronic
               study               patients            clopidogrel, no benefit with reloading
             population
                                                     • Clopidogrel reloading may be of benefit in
                                                       unstable patients
                  Clopidogrel      No reload
                    reload                           • Favorable bleeding profile with reloading


                                                      Presented by Dr. Germano Di Sciascio at
                                                      SCAI-ACC i2 Summit/ACC 2008
                                                     ASTRAL
         Trial design: Patients with significant renal artery stenosis were randomized to angioplasty
         and/or stenting plus medical therapy (n = 403) or medical therapy alone (n = 403) and
         followed for 27 months.

                                                              Results
                 (p = ns)               (p = ns)              • Baseline creatinine, 2.02 mg/dl; glomerular
                                                                filtration rate, 40 ml/min; mean stenosis, 76%;
                                                                anti-hypertensive medications, 2.8 per patient
    16                                 12       14
                                                              • 93% of revascularized patients received a stent
                7.4    8.2
                                                              • At follow-up, no difference in creatinine, blood
%   8                                                           pressure, time to first renal event, or mortality
                                                                (p = ns for all outcomes)
    0
                CV mortality
            Cardiovascular
                                  Hospitalization for fluid
                                Hospitalization for           Conclusions
                                 overload or heart failure
               mortality         fluid overload or            • Renal artery revascularization is not superior
                                    heart failure               to medical therapy alone
                                                              • Renal artery stenting does not reduce
                                                                creatinine, blood pressure, time to first renal
                     Renal              Medical                 event, adverse cardiac events, or mortality
                    stenting            therapy

                                                                Presented by Dr. Philip Kalra at SCAI-ACC i2
                                                                Summit/ACC 2008
                                            ATHEROMA
Trial design: Patients with carotid stenosis >40% and who demonstrated intraplaque
accumulation of ultra small super-paramagnetic iron oxide (USPIO) on MRI at baseline
were randomized to either 10 mg or 80 mg atorvastatin daily for 12 weeks.

                                                            Results
                       (p < 0.0001)                         • Significant reduction from baseline in USPIO-defined
                                                              signal intensity was observed in 80 mg group at 6
                                                              and 12 weeks; no difference was observed in low-
          0.5                                                 dose arm at 6 and 12 weeks
                       0.20    0.038                        • Mean signal difference at 12 weeks between the two
          0.4
                                                              groups was 0.24 (p < 0.0001)
          0.3
  Units




                                                            Conclusions
          0.2                                               • Aggressive lipid-lowering therapy with 80 mg of
                                                              atorvastatin daily is associated with significant
          0.1                                                 reduction in USPIO-defined inflammation in
                                                              carotid plaques
           0
                                                            • USPIO-defined inflammation represents a novel
                Signal intensity at 12 weeks
                                                              imaging biomarker
          Atorvastatin 10 mg           Atorvastatin 80 mg
               (n = 20)                     (n = 20)
                                                             Presented by Dr. Tjun Tang at SCAI-ACC i2 Summit/ACC
                                                             2008
                                                 BRAVE 3
    Trial design: Patients with STEMI undergoing PCI were randomized to either abciximab or
    unfractionated heparin (UFH), after pretreatment with 600 mg of clopidogrel. LV infarct size
    was evaluated at 5-7 days.

                                                     Results
                                                     • Mean final infarct size: 15.7% vs. 16.5% in the
                   (p = 0.47)                          abciximab and control groups (p = 0.47)
    20                                               • Death, MI, stroke or urgent revascularization:
                 15.7      16.5                        5.0% vs. 3.8% in the abciximab and control
    18                                                 groups (p = 0.39)

    16
%                                                    Conclusions
    14
                                                     • No difference in infarct size or clinical outcomes
                                                       with abciximab in patients with STEMI
    12
                                                       undergoing PCI following pretreatment with 600
                                                       mg of clopidogrel
    10
                Final infarct size


             Abciximab               Placebo
              (n = 401)              (n = 399)
                                                     Presented by Dr. Julinda Mehilli at SCAI-ACC i2
                                                     Summit/ACC 2008
                                                      ECLIPSE
      Trial design: Patients with diagnostic and interventional coronary/peripheral procedures
      were randomized to the ExoSeal closure device (n = 267) or manual pressure (n = 134).


                                                            Results
                                                            • 50% interventional procedures; 89% device
                                                              success
           (p < 0.0001)                     (p = 0.67)
                                                            • Time to hemostasis: 4.4 min for closure device
                                                              and 20.1 min for manual pressure (p < 0.0001)
           4.4          20.1               1.9      0.7     • Hematoma >6 cm: 1.9% vs. 0.7% (p = 0.67),
30
                                 2                            respectively
15   min                         1
                                     %

 0                               0                          Conclusions
            Time to hemostasis
             Time to                     Large (>6 cm)
                                           Large hematoma
                                                            • The ExoSeal closure device reduces time to
           hemostasis                     hematoma
                                                              hemostasis compared with manual pressure
                                                            • No adverse events in either group
                                                            • Nonsignificant increase in large hematomas
                    Closure                 Manual
                                                              with ExoSeal closure device
                    device                 pressure

                                                             Presented by Dr. Shing-Chiu Wong at
                                                             SCAI-ACC i2 Summit/ACC 2008
                                              ENHANCE
         Trial design: Patients with heterozygous familial hypercholesterolemia were randomized to
         treatment with ezetimibe/simvastatin 10/80 mg or simvastatin 80 mg alone. Mean change in
         intima-media thickness (IMT) was measured in the carotid arteries over 2 years.



              (p < 0.01)               (p = 0.20)
                                                        Results
                                                        • Mean carotid IMT 0.0058 ± 0.0037 mm in the
                                        4.7               simvastatin arm vs. 0.0111 ± 0.0038 mm in
                                 5                        the ezetimibe/simvastatin arm (p = 0.29)
                      193        4                      • Mean LDL levels 192.7 mg/dl (39% ↓) in
        200
                                                          simvastatin arm, 141.3 mg/dl in the
                141                           2.8         ezetimibe/simvastatin arm (56% ↓) (p < 0.01)
        150                      3
mg/dl




                                %
        100                      2                      Conclusions
                                                        • No additional benefit in carotid IMT reduction at
        50                       1                        2 years with ezetimibe/simvastatin compared
                                                          with high-dose simvastatin alone
         0                       0
                                                        • LDL lowering greater with ezetimibe/simvastatin
              LDL cholesterol    New plaque formation
                                                        • Clinical outcomes and adverse events similar
                  Ezetimibe/         Simvastatin
                  Simvastatin         (n = 363)
                   (n = 357)
                                                        Kastelein JJ, et al. N Engl J Med 2008;358:1431-43
                                        GENESIS
Trial design: In this single-blinded study, patients were randomized 2:2:1 to CORIO
(pimecrolimus-eluting), SYMBIO (pimecrolimus- and paclitaxel-eluting), or CoStar
(paclitaxel-eluting) control arm.

                                                 Results
                                                 • In-stent late loss: 1.40 ± 0.67 mm, 0.96 ± 0.73
                                                   mm, and 0.58 ± 0.58 mm in CORIO, SYMBIO,
                                                   and CoStar arms, respectively
                39.8   20.4   7.1
                                                 • 6-month MACE: 39.0% vs. 14.4% vs. 2.0% for
    40                                             CORIO, SYMBIO, and CoStar arms

    30
                                                 Conclusions
    20                                           • First trial to successfully demonstrate dual drug
%                                                  delivery in patients with CAD undergoing PCI
    10                                           • Pimecrolimus ± paclitaxel is associated with
                                                   higher incidence of in-stent restenosis and
     0                                             MACE compared with paclitaxel alone
                In-stent restenosis
     CORIO              SYMBIO        CoStar
    (n = 100)           (n = 101)     (n = 49)
                                                 Presented by Dr. Stefan Verheye at SCAI-ACC i2
                                                 Summit/ACC 2008
                                                        HAT
        Trial design: Intermediate-risk patients after an anterior myocardial infarction were
        randomized to automated external defibrillator (AED) and cardiopulmonary resuscitation
        (CPR) (n = 3,495) versus CPR alone (n = 3,506) and followed for 37 months.

                                                          Results
                                                          • All-cause mortality: 6.4% for AED and CPR
                       (p = 0.77)                           vs. 6.5% for CPR alone (p = 0.77)
                                                          • 37.6% of deaths were due to tachyarrhythmia,
                     6.4             6.5                    with remainder due to heart failure or
    8
                                                            noncardiac causes
%
                                                          • Only 8 patients in each group were
    4                                                       resuscitated at home


    0                                                     Conclusions
                      All-cause mortality
                   All-cause mortality                    • AED and CPR are not superior to CPR alone
                                                            in intermediate-risk patients after an MI
                                                          • Relatively few deaths in this population are
                AED and                     CPR alone       due to tachyarrhythmia
                 CPR



                                                          Bardy GH, et al. N Engl J Med 2008;358:1793-804.
                                                     HORIZON-HF
       Trial design: Decompensated heart failure patients were randomized to Istaroxime, an
       inotropic and lusitropic agent (n = 29 for 0.5 mcg/kg/min; n = 30 for 1.0 mcg/kg/min; n = 30
       for 1.5 mcg/kg/min) or placebo (n = 31).

                                                                 Results
                  (p = 0.04)                    (p = 0.02)       • Systolic blood pressure: ↑ 10 mm Hg with 1.5
                                                                   mcg/kg/min Istaroxime and ↑ 0.6 mm Hg with
                                                                   placebo (p < 0.001)
                                                                 • Cardiac index: +0.3 L/min/m2 vs. -0.01
                  +0.3   -0.01                  -14.1   +3.9
                                                                   L/min/m2 (p = 0.04), respectively
       L/min/m2




0.4
                                                                 • LV end-diastolic volume: -14.1 ml vs. +3.9 ml
0.2                                 10                             (p = 0.02), respectively
                                         ml




  0                                  0

-0.2                             -10
                                                                 Conclusions
                                 -20
                                                                 • In this dose-finding study, Istaroxime 1.5
           Cardiac index                      Left ventricular     mcg/kg/min may be beneficial in improving
                                               end-diastolic       hemodynamics and diastolic function in
                                                  volume           patients with decompensated heart failure

                  Istaroxime, 1.5                Placebo
                    mcg/kg/min

                                                                 Presented by Dr. Mihai Gheorghiade at the
                                                                 SCAI-ACC i2 Summit/ACC 2008
                                                 HYVET
     Trial design: Hypertensive geriatric (age >80 years) patients were randomized to
     indapamide SR 1.5 mg or to placebo. Clinical outcomes were evaluated at 2 years.


                                                    Results
        (p = 0.06)                  (p = 0.02)      • Trial was terminated early
                                                    • Stroke ↓ 30% (p = 0.06), mortality ↓ 21% (p =
 5                             15                     0.02), heart failure ↓ 64% (p < 0.001) in
          2.6    3.6                10.1 12.3
                                                      indapamide arm compared with placebo
 4                                                  • Number needed to treat at 2 years: 94 for
                               10                     stroke, 40 for mortality
 3
%                              %
 2                                                  Conclusions
                               5
                                                    • Significant mortality benefit with treatment of BP
 1                                                    >160 mm Hg in patients older than 80 years
 0                             0                    • Newer guidelines will need to consider this
                                                      group of patients specifically
           Strokes                  Mortality

                Indapamide            Placebo
                 (n = 1,933)         (n = 1,912)

                                                    Presented by Dr. Nigel Beckett at SCAI-ACC i2
                                                    Summit/ACC 2008
                                       ISAR-REACT 3
      Trial design: Troponin-negative patients undergoing PCI were randomized to either
      bivalirudin or unfractionated heparin (UFH), after pretreatment with 600 mg of clopidogrel.
      Clinical outcomes were evaluated at 30 days.

                                                      Results
                                                      • Primary endpoint: death, MI, urgent target
           (p = 0.57)                (p = 0.008)        vessel revascularization, or in-hospital major
                                                        bleeding was similar between the bivalirudin
 10       8.3 8.7              5      3.1 4.6           (8.3%) and UFH (8.7%) arms (p = 0.57)
  9                                                   • Bleeding significantly ↓ with bivalirudin
  8                            4                        compared with UFH: major (33%), minor (31%)
  7
  6                            3
                                                      Conclusions
%5                            %
  4                            2                      • Bivalirudin is not superior to UFH as adjunct
  3                                                     anticoagulation therapy for troponin-negative
  2                            1                        patients undergoing PCI, who were pretreated
                                                        with 600 mg of clopidogrel
  1
  0                            0                      • Bleeding was significantly reduced with
      Composite endpoint           Major bleeding       bivalirudin compared with UFH

                Bivalirudin            UFH
                (n = 2,289)         (n = 2,281)
                                                      Presented by Dr. Adnan Kastrati at SCAI-ACC i2
                                                      Summit/ACC 2008
                                       MEND-CABG II
        Trial design: Intermediate-risk patients undergoing CABG were randomized to MC-1 (n =
        1,519) or placebo (n = 1,504) and followed for 30 days after surgery.


                                                       Results
                                                       • Median aortic cross-clamp time of 1.0 hour,
                (p = 0.03)           (p = 0.44)          internal mammary artery graft used in 90%
                                                       • Death or nonfatal MI: 9.3% in MC-1 group and
                                                         9.0% in control (p = 0.76)
                                     1.9    1.5
    2                                                  • All-cause mortality: 1.0% vs. 0.3% at 4 days
               1       0.3                               (p = 0.03) and 1.9% vs. 1.5% at 30 days (p =
%                                                        0.44), respectively
    1

                                                       Conclusions
    0                                                  • In intermediate-risk patients undergoing
             4-day mortality
               4 day mortality      30 day mortality
                                 30-day mortality        CABG, MC-1 is not superior to placebo
                                                       • MC-1 does not reduce death or MI at 30 days
                   MC-1              Placebo           • MC-1 increased 4-day mortality; however, no
                                                         difference at 30 days


                                                       Alexander JH, et al. JAMA 2008;299:1777-87
                                          MOMENTUM
       Trial design: Patients with refractory heart failure symptoms were randomized to the Orqis
       continuous aortic flow augmentation device for 4 days (superimposing low-level continuous
       flow on pulsatile flow) (n = 109) or continued medical management (n = 59).

                                                      Results
                                                      • Cardiac index: increased to more than 2.4
               (p = 0.005)         (p = 0.005)          L/min/m2 (p < 0.0001) with the device
                                                      • Death or heart failure hospitalization at 65
                                                        days: similar between the two groups (p = ns)
             16.5   5.1            26.6    8.5
  30                                                  • Major bleeding: 16.5% vs. 5.1% (p = 0.05),
                                                        respectively


% 15
                                                      Conclusions
                                                      • Continuous aortic flow augmentation for 4
                                                        days increases cardiac index, although death
   0
            Major bleeding
             Major bleeding     Minor bleeding
                                  Minor bleeding
                                                        or heart failure hospitalization is similar
                                                      • Major and minor bleeding are increased with
               Continuous                               the device
                                     Medical
               aortic flow
                                   management
              augmentation

                                                       Presented by Dr. Barry Greenberg at SCAI-ACC i2
                                                       Summit/ACC 2008
                                                   ONTARGET
     Trial design: Patients at high risk for cardiovascular events, but without heart failure, were
     randomized to telmisartan, ramipril, or the combination. Patients were followed for a
     median of 56 months.

                                                                     Results
         (p < 0.004*)                           (p = ns)             • Telmisartan (16.7%) noninferior; combination
                                                                       (16.3%) not superior to ramipril (16.5%) for primary
                                                                       endpoint (CV death, MI, stroke, heart failure)
        16.7 16.3 16.5                     11.6 12.5 11.8
20                               15                                  • Greater incidence of hypotension in combination
                                                                       (4.8%) and telmisartan (2.7%) groups, compared
                                                                       with ramipril group (1.7%) (p < 0.001)
%                                10
10                               %
                                 5                                   Conclusions
                                                                     • Either telmisartan or ramipril, but not both, can
0                                 0                                    be used in hypertensive patients at high risk for
                                                                       cardiovascular events
       Primary endpoint                         Mortality
                                                                     • Side effects greater with combination therapy
       Telmisartan           Combination              Ramipril
        (n = 8,542)           (n = 8,502)            (n = 8,576)

* Telmisartan vs. ramipril for noninferiority
                                                                   The ONTARGET investigators. N Engl J Med 2008;358:1547-59
                                           ON-TIME 2
     Trial design: STEMI patients who presented to a non-PCI center were randomized to
     tirofiban prior to transfer for primary PCI (n = 491) or placebo with provisional tirofiban in
     the catheterization laboratory (n = 493) and followed for 30 days.

                                                       Results
                                                       • Mean transportation distance: 25 km
              (p = 0.026)           (p = 0.14)
                                                       • >3 mm ST-elevation post-PCI: 36.6% with
                                                         tirofiban and 44.3% with placebo (p = 0.026)
             36.6   44.3                               • Mortality: 2.3% vs. 4.0% (p = 0.14), respectively
    50
                                                       • Major bleeding: 4.0% vs. 2.9% (p = 0.36),
                                                         respectively
%
    25
                                     2.8   4.0
                                                       Conclusions
                                                       • In STEMI patients, tirofiban prior to transfer for
    0
                                                         PCI is beneficial
         >3 mm ST-elevation
             ST-elevation            mortality
                                   Mortality
             post-PCI                                  • Upstream tirofiban reduces ST-elevation post-
                                                         PCI and nonsignificantly decreases mortality
             Upstream               Provisional        • Potential for increased bleeding with upstream
             tirofiban               tirofiban           tirofiban


                                                       Presented by Dr. Christian Hamm at SCAI-ACC i2
                                                       Summit/ACC 2008
                                                                   PERISCOPE
                               Trial design: Patients with CAD and diabetes were randomized to receive either
                               glimepiride or pioglitazone. Baseline and 18-month IVUS measurements were performed.


                                                                              Results
                                      (p = 0.002)                (p = 0.37)   • Least square mean change in % atheroma volume
                                                                                from baseline ↑ 0.73% in the glimepiride arm while it
                              0.8       0.73 -0.16               0.36 1.1       ↓ 0.16% in the pioglitazone arm (p = 0.002)
% change in atheroma volume




                                                                              • Composite endpoint: CV death, nonfatal MI, or stroke
                              0.6                       1.2                     was similar between the glimepiride (2.2%) and
                                                                                pioglitazone (1.9%) arms (p = 0.78).
                              0.4
                                                                              • CRP, triglycerides ↓, HDL ↑ with pioglitazone
                                                        0.8
                              0.2
                                                        %                     Conclusions
                                                        0.4                   • Pioglitazone is better than glimepiride in reducing
                               0
                                              1                                 the progression of CAD in diabetic patients, in the
                                                                                background of optimal medical therapy
                              -0.2
                                                                              • Pioglitazone has a favorable impact on
                                                        0
                                                                                biochemical parameters, with increased side
                                     Primary endpoint          CV mortality
                                                                                effects
                                      glimepiride             Pioglitazone
                                       (n = 273)                (n = 270)      Nissen S, et al. JAMA 2008;299:1561-73
                                          PROTECT Pilot
    Trial design: Decompensated heart failure patients were randomized to rolofylline, an
    adenosine A1 receptor antagonist (30 mg, n = 74; 20 mg, n = 75; 10 mg, n = 74), or
    placebo (n = 78).

                                                    Results
                               (p = ns)             • Fewer patients with rolofylline 30 mg
                                                      experienced >0.3 mg/dl increase in serum
                                                      creatinine compared with placebo (p < 0.05)
                                                    • Death or rehospitalization for heart failure:
                          19                33
    40                                                19% with rolofylline 30 mg and 33% for
                                                      placebo (p = ns)
                                                    • No seizures in either group
%
    20

                                                    Conclusions
     0                                              • Acute decompensated heart failure patients:
                  Death or rehospitalization
                   death or hospitalization           less renal dysfunction with rolofylline 30 mg
                      for heart failure             • Possible reduction in death or
                                                      rehospitalization for heart failure with
            Rolofylline                   Placebo     rolofylline


                                                        Presented by Dr. Barry Massie at the SCAI-ACC i2
                                                        Summit/ACC 2008
                                           REVERSE
    Trial design: Patients with LV dysfunction (NYHA class I-II) and wide QRS were
    randomized to cardiac resynchronization therapy (CRT) (n = 419) or optimal medical
    therapy (n = 191).

                                                  Results
                                                  • Patients worsened: 16% with CRT vs. 21% with
                         (p = 0.1)                  optimal medical therapy (p = 0.1)
                                                  • LV end-systolic volume index: decreased 18.4
    30                                              ml/m2 vs. 1.3 ml/m2 (p < 0.0001), respectively
                    16               21
%                                                 • Risk of heart failure hospitalization reduced with
    20
                                                    CRT (p = 0.03)

    10
                                                  Conclusions
     0
                                                  • CRT for mild heart failure does not reduce the
                     Percentage worsened
                  Percentage worsened               percentage of patients that clinically worsen
                                                  • CRT improves LV end-systolic volume index
                                                    and reduces the risk of hospitalization
              CRT                    Medical        compared with optimal medical therapy
                                     therapy



                                                   Presented Dr. Cecilia Linde at SCAI-ACC i2
                                                   Summit/ACC 2008
                                                                    SEISMIC
     Trial design: Patients with myocardial scar were randomized to autologous skeletal
     myoblast cells (n = 31) or medical therapy (n = 16) and followed for 6 months.


                                                                           Results
                      p = ns                               p = ns
                                                                           • In treatment group, 8.3 years since MI and
                                                                             31% ejection fraction
                                                                           • Percentage with serious adverse event: 50%
                                                                             in myoblast group and 36% in control (p = ns)
60
               50                36                       +0.3      -0.1
                                                                           • Change in ejection fraction: ↑ 0.3% vs. ↓ 0.1%
                                               0.4
                                                                             (p = ns), respectively
30   %
                                               0.2    %
 0                                               0
         Patients with serious adverse event

                                               -0.2                        Conclusions
         Serious adverse                              Change in ejection
                                                                           • In this small study, implantation of autologous
              events                                      fraction
                                                                             skeletal myoblast cells after MI is feasible
                                                                           • No apparent excess in serious adverse events
                     Autologous                           Medical          • Potential small increase in ejection fraction
                      skeletal                            therapy            with myoblast cells at 6 months follow-up
                      myoblast
                        cells
                                                                            Presented by Dr. Patrick Serruys at SCAI-ACC i2
                                                                            Summit/ACC 2008
                                                      SPIRIT II
     Trial design: This was a randomized study designed to evaluate the safety and efficacy of
     the XIENCE V everolimus-eluting stent compared with the TAXUS paclitaxel-eluting stent
     among patients with de novo coronary lesions.

                                                            Results
             (p = 0.61)                      (p = ns)      • In-stent late loss 0.11 mm (everolimus) and 0.36 mm
                                                             (paclitaxel) at 6 months (p < 0.001). Similar at 2
              0.33 0.34                    0.36 1.1          years (0.33 mm vs. 0.34 mm, p = 0.61)
     0.5
                                                           • MACE at 2 years: 6.6% vs. 11.0% (p = 0.31)
                                1.6
     0.4                                                   • Stent thrombosis at 2 years: 0.9% vs. 1.4% (p = ns)

                                1.2
     0.3
                                %                           Conclusions
mm




     0.2                        0.8                        • Benefit in in-stent late lumen loss was seen with
                                                             everolimus compared with paclitaxel at 6 months,
                                                             but not seen at 2 years
     0.1                        0.4
                                                           • Clinical outcomes were similar to paclitaxel-eluting
                                                             stents at 2 years
     0                              0
                   1
                                                           • Long-term data on stent performance necessary
           In-stent late loss           Stent thrombosis

             XIENCE V                      TAXUS
             (n = 223)                     (n = 77)         Presented by Dr. Patrick Serruys at SCAI-ACC i2
                                                            Summit/ACC.08
                                                  STRADIVARIUS
      Trial design: Obese patients with metabolic syndrome were randomized to the
      cannabinoid type 1 receptor inhibitor rimonabant 20 mg daily (n = 422) or placebo (n = 417)
      and underwent IVUS examination after 18 months of treatment.

                                                                         Results
                (p = 0.22)                       (p < 0.001)             • Percent atheroma volume: +0.25% for
                                                                           rimonabant vs. +0.51% for placebo (p = 0.22)
                                                                         • Psychiatric symptoms: 43% vs. 28% (p < 0.001),
                                                                           respectively
                                                                         • Gastrointestinal track symptoms: 34% vs. 18% (p
            0.25             0.51                 43           28
                                                                           < 0.001), respectively
0.6                                     50


0.3   %                                 25   %
                                                                         Conclusions
 0                                      0
              Percent atheroma volume
          Percent atheroma
                                                  Psychiatric symptoms
                                                 Psychiatric             • Rimonabant is not superior to placebo in
               volume                            symptoms                  reducing percent atheroma volume in obese
                                                                           patients with metabolic syndrome
                                                                         • Rimonabant results in more psychiatric and
                                                                           gastrointestinal track symptoms compared
                                                                           with placebo
               Rimonabant                         Placebo


                                                                         Nissen SE, et al. JAMA 2008;299:1547-60
                                                    TAPAS
      Trial design: Patients with STEMI were randomized to thrombus aspiration prior to PCI (n
      = 535) or standard PCI without aspiration (n = 536).


                                                       Results
             (p < 0.001)             (p = 0.07)        • Good myocardial blush: 46% with aspiration
 60                                                      and 32% with standard PCI (p < 0.001)
           46                                          • ST-segment resolution: 57% and 44%,
                                                         respectively (p < 0.001)
                  3                                    • Death: 2.1% and 4.0%, respectively (p = 0.07)
%30               2


                                            4          Conclusions
                                  2.1
  0                                                    • In STEMI, thrombus aspiration prior to PCI is
                                                         superior to standard PCI without aspiration
        Good myocardial           Mortality            • Thrombus aspiration improves myocardial
            blush                                        blush and ST-segment resolution

            Thrombus aspiration         PCI alone      • Thrombus aspiration may improve adverse
                  and PCI               (n = 536)        events including survival
                 (n = 535)
                                                       Svilaas T, et al. N Engl J Med 2008;358:557-67
                                TRANSFER-AMI
     Trial design: Patients with STEMI who presented to centers where timely primary PCI was
     not feasible were randomized to a pharmacoinvasive strategy (emergent transfer for PCI
     within 6 hours of fibrinolysis) or to standard treatment after fibrinolysis.



       (p = 0.0013)             (p = 0.94)        Results
                                                  • Primary endpoint: death, MI, heart failure,
20                          5                       severe recurrent ischemia, or shock 10.5% in
                16.5                                pharmacoinvasive arm vs. 16.5% in standard
                            4   3.7   3.6           treatment arm (p = 0.0013)
                                                  • Reinfarction: 3.3% vs. 6.0% (p = 0.044)
%        10.5               3
10                      %                         • Recurrent ischemia: 0.2% vs. 2.2% (p = 0.02)
                            2
                                                  Conclusions
                            1                     • Pharmacoinvasive approach safe and
                                                    efficacious compared with treatment with
0                           0                       thrombolytics and transfer for rescue PCI only
     Primary endpoint           Mortality         • Optimal window: 6 hours

           Pharmacoinvasive       Standard
                  arm              therapy
               (n = 522)          (n = 508)
                                                  Presented by Dr. Warren Cantor at
                                                  SCAI-ACC i2 Summit/ACC.08
                                              VICTORY
    Trial design: Type 2 diabetic patients with prior CABG were randomized to rosiglitazone (n
    = 98) or placebo (n = 95) after baseline coronary angiography and IVUS.


                                                    Results
                         (p = 0.22)                 • Years since CABG: 3.9 in rosiglitazone group
                                                      and 3.7 in placebo group

    4                                               • Saphenous vein graft plaque volume: +0.9%
                       0.9              2.8           vs. +2.8% (p = 0.22), respectively
                                                    • Mortality: no deaths in either group
%   2                                               • MI: 0 vs. 1, respectively


    0                                               Conclusions
               Saphenous vein graft plaque volume
              Change in saphenous vein graft        • Rosiglitazone does not change saphenous
                      plaque volume                   vein graft plaque volume in type 2 diabetic
                                                      patients after CABG
                                                    • The incidence of mortality and MI is similar
           Rosiglitazone              Placebo         between rosiglitazone and placebo


                                                     Presented by Dr. Olivier Bertrand at SCAI-ACC i2
                                                     Summit/ACC 2008
                                          VISION 302
    Trial design: Patients with known or suspected CAD undergoing a pharmacologic stress
    test with SPECT imaging were stratified and randomized to binodenoson or adenosine for
    the determination of the magnitude of ischemia.

                                                   Results
        (p = 0.004)                  (p < 0.05)    • Binodenoson was noninferior to adenosine. The
                                                     mean paired summed difference scores
          0       3                  30     50       difference of binodenoson vs. adenosine images
    3                           50                   was -0.09 (95% CI -0.44 to 0.27)
                                                   • 2nd or 3rd degree AV block was 0% with
                                40
                                                     binodenoson and 3% with adenosine (p = 0.004)
    2
%                               30
                            %                      Conclusions
    1                           20                 • Binodenoson (selective A2A receptor agonist) is as
                                                     effective as adenosine (nonselective agonist) as
                                10                   agent for detection of ischemia in pharmacologic
    0                                                stress tests in suspected/known CAD patients
                            0                      • Side effects are fewer and less intense with
    2nd or 3rd degree AV block       Flushing        binodenoson compared with adenosine
              Binodenoson             Adenosine
                (n = 402)              (n = 404)
                                                   Presented by Dr. James Udelson at SCAI-ACC i2
                                                   Summit/ACC 2008
 ESC Congress 2008

Clinical Trial Summary Slides
                                                   3T/2R
        Trial design: Patients undergoing PCI were screened for poor response to aspirin and/or
        clopidogrel. Poor responders were then randomized to tirofiban (n = 132) or placebo (n =
        131). Follow-up was 30 days.

                                                       Results
                                                       • Troponin I or T >3x ULN at 48 hours: 20% for
               (p = 0.009)           (p = 0.006)
                                                         tirofiban vs. 35% for placebo (p = 0.009)
                                                       • MACE at 30 days: 21% vs. 37% (0.006),
                                             37          respectively
40                    35
                                                       • TIMI major bleeding at 30 days: 0 vs. 0
%
              20                     21
20
                                                       Conclusions
                                                       • Tirofiban is beneficial at reducing MI within 48
    0                                                    hours after PCI among poor responders to
                                                         aspirin and/or clopidogrel
             Troponin > T
          Troponin I or3x >3x    MACE MACE days
                                      at 30
           ULN at 48 hours                             • Tirofiban also reduced MACE at 30 days
                                                       • There were no major bleeds in either group
               Tirofiban           Placebo


                                                       Presented by Dr. Marco Valgimigli at ESC 2008
                                             APPRAISE-1
        Trial design: Patients recovering from an ACS were randomized to apixaban 10 mg daily
        (n = 318), apixaban 2.5 mg twice daily (n = 317), or placebo (n = 611). Study medications
        were administered for 6 months.

                                                       Results
                 p = 0.005 for          p = 0.09 for   • ISTH major or CRNM bleeding: 7.9% for 10
                  high-dose            low-dose vs.      mg apixaban, 5.7% for 5 mg apixaban, 3% for
                 vs. placebo              placebo        placebo (p = 0.005 for high-dose vs. placebo
                                                         and p = 0.09 for low-dose vs. placebo)
                                                       • Death, MI, recurrent ischemia, or stroke:
                                                         6.0%, 7.6%, 8.7% (p = 0.07 for high-dose vs.
    9               7.9
                                                         placebo and p = 0.21 for low-dose vs.
                                                         placebo), respectively
    6
                                 5.7
%
                                             3         Conclusions
    3
                                                       • This dose-finding study reveals that bleeding
                                                         is increased among patients with a recent
    0
                                                         ACS with higher doses of apixaban compared
                      ISTH major or clinically
                     ISTHmajor or CRNM bleeding          with placebo
                   relevant nonmajor bleeding
                                                       • Although this study was not powered for
                                 Apixaban 5 mg           efficacy, adverse events appeared to be
            Apixaban
                                                         lowest with 10 mg apixaban
             10 mg
                                 Placebo
                                                       Presented by Dr. John Alexander at ESC 2008
                                                ATHENA
     Trial design: High-risk patients with paroxysmal or persistent atrial fibrillation or flutter were
     randomized to dronedarone 400 mg twice daily or placebo. Patients were followed for a
     mean of 21 months.

                                                        Results
          (p = 0.18)               (p = 0.027)         • Dronedarone associated with a 24% ↓ in cardiac
                                                         hospitalizations or death vs. placebo (p<0.001)
                                                       • Overall mortality similar (p = 0.18), cardiovascular
10                            10                         mortality lower with dronedarone (p = 0.03)
                                                       • Higher GI side-effects and increased creatinine with
                                                         dronedarone, other side-effects similar
                 6.0
          5.0                                           Conclusions
5                             5
                              %




                                                        • Dronedarone is safe and effective in the chronic
%




                                          1.8             management of atrial fibrillation in high-risk
                                   1.2                    patients

 0                             0                        • Head-to-head comparison with amiodarone
                                                          awaited
          Mortality                 Stroke
                Dronedarone            Placebo
                 (n = 2301)           (n = 2327)        Presented by Dr. Stefan Hohnloser at the Heart Rhythm
                                                        Society 2008
                                            BEAUTIFUL
     Trial design: Patients with stable CAD and moderate LV dysfunction were randomized to
     the sinoatrial node inhibitor, ivabradine (n = 5,479), or placebo (n = 5,438). Median follow-
     up was 19 months.

                                                          Results
                                                          • Difference in heart rate at 24 months: 5.6 bpm
                (p = 0.94)             (p = 0.55)           lower with ivabradine
                                                          • CV death, MI, or HF: 15.4% for ivabradine vs.
                                                            15.3% for placebo (p = 0.94)
    18
              15.4    15.3
                                                          • All-cause mortality: 10.4% vs. 10.1% (p = 0.55)
%                                    10.4      10.1       • HF admission: 7.8% vs. 7.9% (p = 0.85)
    9


                                                          Conclusions
    0                                                     • Ivabradine produces a sustained reduction in
         CV CV death,HF admission
            death, MI, or MI, HF    all-cause mortality
                                     All-cause              heart rate over long-term follow-up
              admission              mortality            • Among patients with stable coronary disease
                                                            and moderate LV dysfunction, ivabradine does
                                                            not improve mortality, MI, or HF admissions
              Ivabradine             Placebo


                                                          Fox K, et al. Lancet 2008;Aug 31:[Epub before print]
                                                        CARDia
    Trial design: Diabetic patients with multi-vessel disease or complex single-vessel disease,
    but not left main disease, were randomized to either CABG or PCI. Clinical outcomes were
    compared at 12 months.

                                                             Results
                                                             • Primary endpoint (death, MI, stroke) was similar
            (p = 0.63)                     (p = 0.001)         between CABG and PCI (10.2% vs. 11.6%, p = 0.63)
                                                             • Significant ↓ in repeat revascularization in CABG arm
                                    20                         (2% vs. 9.9%, p = 0.001). True in drug-eluting stent
    20
                                                               subset also
                                                             • Trend toward increased CVA in CABG arm (p = 0.09)
    15                              15
                     11.6
%            10.2               %                      9.9   Conclusions
    10                              10
                                                             • Similar incidence of death, MI, or stroke in
                                    5                          diabetics with CABG or PCI
    5
                                             2.0
                                                             • CABG was associated with fewer repeat
    0                               0                          revascularizations compared with PCI
         Primary endpoint                     Repeat         • No difference in death, MI, but trend toward
                                         revascularization     increased stroke with CABG, as suggested by
                     CABG                     PCI
                                                               other studies
                    (n = 254)              (n = 256)
                                                             Presented by Dr. Akhil Kapur at ESC 2008
                                 CARESS-in-AMI
    Trial design: STEMI patients admitted to non-PCI hospitals and initially treated with
    heparin, half-dose reteplase, and abciximab were randomized to immediate transfer for
    urgent PCI (n = 299) or standard therapy with rescue PCI if needed (n = 301).

                                                  Results
                                                  • 86% of the immediate PCI group underwent
         (p = 0.005)          (p = 0.47)            PCI vs. 30% of the standard care group
                                                  • Death, MI, or refractory ischemia at 30 days
                                                    (4.4% vs. 10.7%, p = 0.005)
    12            10.7
                                                  • Refractory ischemia (0.3% vs. 4.0%, p =
                                                    0.003)
     8
%           4.4                3.4
                                                  Conclusions
     4                                2.3
                                                  • STEMI patients treated with half-dose lytics
     0                                              and abciximab did better with immediate
               MACE          Major bleeding         transfer for PCI
                                                  • This approach reduced death, MI, or refractory
                                                    ischemia at 30 days
         Transfer for PCI      Standard therapy
            (n = 299)              (n = 301)      • Benefit driven by reduction in refractory
                                                    ischemia

                                                    Di Mario C, et al. Lancet 2008;371:559-68
                                             DECREASE III
    Trial design: Patients undergoing noncardiac vascular surgery were randomized to
    fluvastatin XL or placebo, in addition to beta-blockers. Clinical outcomes were compared at
    1 month.

                                                          Results
                                                          • Myocardial ischemia was significantly reduced with
            (p = 0.016)                  (p = 0.039)        statin (OR 0.53; 95% CI 0.32-0.88, p = 0.016)
                                                          • LDL (p < 0.001) and hs-CRP (p  0.001) were lower
                                                            in statin arm
    20              19.0            20
                                                          • Incidence of adverse events was similar
    15                              15
%            10.9               %                 10.1
                                                          Conclusions
    10                              10                    • Perioperative statin therapy was associated with
                                                            improved outcomes in high-risk patients
                                            4.8
    5                               5                       undergoing noncardiac vascular surgery
                                                          • Results add to current literature on the benefit of
    0                               0                       statins in the perioperative period
         Myocardial ischemia             CV death or MI
               Fluvastatin XL             Placebo
                  (n = 250)               (n = 247)
                                                          Presented by Dr. Don Poldermans at ESC 2008
                                                         FIRE
       Trial design: STEMI patients were randomized to the fibrin-derived peptide FX04 400 mg
       intravenously (n = 114) versus placebo (n = 120).


                                                           Results
                                                           • Total late enhancement zone at 5 days: 21.7 g
                               (p = 0.36)                    for FX06 vs. 27.3 g for placebo (p = 0.21) and
                                                             at 4 months: 15.4 g vs. 19.3 g (p = 0.36),
      30                                                     respectively
                                            19.3           • LVEF at 4 months: 49% vs. 49%, respectively
      20                15.4
                                                           • Serious adverse events: 18% vs. 24%,
(g)




                                                             respectively
      10


      0                                                    Conclusions
                 total late enhancement zone at 4
                Totallate enhancement zone at 4-months     • This study failed to meet its endpoint of a
                               months                        reduction in total late enhancement
                                                           • There was no difference in LVEF at follow-up
                                                           • There were no important safety signals with
                                                             the use of this agent
                FX04                Placebo

                                                           Presented by Dr. Dan Atar at ESC 2008
                          GISSI-HF: n-3 PUFA Study
  Trial design: Patients with symptomatic CHF were randomized to 1 g n-3 PUFA daily or
  placebo, in addition to optimal medical treatment. Clinical outcomes were compared at 12
  months.

                                                        Results
                                                        • No difference between the two arms for primary
        (p = 0.12)                    (p = 0.013)         endpoint (death), but significant difference noted on
                                                          multivariate analysis (HR 0.91, 95.5% CI 0.83-1.0; p
                                                          = 0.041)
  30           29.1           20
        27.3                                            • No difference in the incidence of first admission for
                                                          heart failure, but fewer admissions for arrhythmia
                              15                          related issues (p = 0.013)
% 20                      %                             Conclusions
                              10
                                                        • No significant difference in mortality in the n-3
  10                                                      PUFA arm, compared with placebo in patients with
                              5         3.0   4.0
                                                          symptomatic heart failure, on optimal treatment
  0                           0                         • However, multivariate analysis showed n-3 PUFA
                                   Arrhythmia related     was associated with small reduction in mortality
         Mortality
                                     hospitalization      (absolute RR 1.8%) compared with placebo

             n-3 PUFA                 Placebo
                                                        • Exact mechanism is unclear, although reduction in
            (n = 3,494)              (n = 3,481)          readmission for arrhythmias was noted
                                                        GISSI-HF Investigators. Lancet 2008;Aug 31:[Epub]
                             GISSI-HF: Rosuvastatin Study
         Trial design: Patients with chronic symptomatic HF were randomized to rosuvastatin 10
         mg daily (n = 2,285) or placebo (n = 2,289). Median follow-up, 3.9 years.


                                                                   Results
                (p = 0.94)                 (p = 0.90)              • All-cause mortality: 29% with rosuvastatin vs.
                                                                     28% with placebo (p = 0.94)
                                                                   • Death or hospital admission for cardiovascular
    60                                     57       56               reasons: 57% vs. 56% (p = 0.90), respectively
                                                                   • Sudden cardiac death: 9.6% vs. 8.6% (p =
%                29       28                                         0.26), respectively
    30



    0
              All-cause mortality   Death or hospital admission
                                                                   Conclusions
                 All-cause           Death or hospital
                 mortality
                                     for cardiovascular reason
                                    admission for CV               • Rosuvastatin 10 mg daily is not beneficial at
                                       reasons                       reducing cardiac outcomes among patients
                                                                     with chronic symptomatic HF
                                                                   • This study should not temper enthusiasm for
                 Rosuvastatin            Placebo                     statins in indicated situations like ACS


                                                                  GISSI-HF Investigators. Lancet 2008;Aug 31:[Epub]
                                             IBIS-2
      Trial design: Patients with CAD were randomized to darapladib 160 mg daily (n = 175) vs.
      placebo (n = 155). Patients underwent IVUS of a nonintervened segment at baseline and at
      12 months.

                                                   Results
                p = 0.71,       p = 0.009,         • Lp-PLA2 reduced 59% by darapladib (p <
              change with      change with           0.001)
               darapladib        placebo
                                                   • Plaque deformability: similar between the
                                                     groups at follow-up (p = 0.22)
                                                   • Necrotic core volume: -0.5 mm3 with
      6                                              darapladib (p = 0.71); +4.5 mm3 with placebo
                                  4.5                (p = 0.009)
      4                                            • MACE: 17% vs. 19% (p = ns), respectively
mm3




      2
                                                   Conclusions
                     -0.5
      0                                            • Treatment with the Lp-PLA2 inhibitor
                                                     darapladib does not affect plaque
      -2                                             deformability
                 Change in necrotic core
                  volume at follow-up              • Darapladib appears to stabilize the necrotic
                                                     lipid core
            Darapladib            Placebo
                                                   • Similar adverse events between the groups

                                                   Serruys PW, et al. Circulation 2008;Sep 1:[Epub]
                                                LEADERS
         Trial design: Patients with stable coronary disease or ACS were randomized to the
         biolimus-eluting stent with a biodegradable polymer (n = 857) or the sirolimus-eluting stent
         with a durable polymer (n = 850). Follow-up was for 9 months.

                                                          Results
              (p = 0.003 for                              • Successful stent implantation: 97.5% for
             non-inferiority)         (p = 0.84)
                                                            biolimus vs. 95.7% for sirolimus (p = 0.05)
                                                          • Death, MI, or TVR: 9.2% vs. 10.5% (p = 0.003
                       10.5                                 for non-inferiority), respectively
    12
                9.2
                                                          • Stent thrombosis: 1.9% vs. 2.0% (p = 0.84),
                                                            respectively
%   6
                                               2.0        Conclusions
                                      1.9
                                                          • Biolimus-eluting stent is non-inferior to
    0                                                       sirolimus-eluting stent for death, MI, or TVR
               Death, MI, TVR        Stent thrombosis
                                        Stent
            Death, MI, urgent                             • Higher rate of successful implantation with the
            revascularization       thrombosis
                                                            biolimus-eluting stent
                                                          • Theoretically, a biodegradable polymer could
             Biolimus-                Sirolimus-
                                                            decrease late stent thrombosis; however,
            eluting stent            eluting stent
                                                            longer-term follow-up is needed


                                                        Windecker S, et al. Lancet 2008;Sept 1:[Epub before print].
                                                      PIHRATE
     Trial design: Patients with STEMI were randomized to aspiration thrombectomy plus PCI
     (n = 102) versus primary PCI alone (n = 94). Follow-up was 6 months.


                                                             Results
                                                             • ST-resolution at 60 minutes: 50% with
                                                               thrombectomy vs. 41% with primary PCI (p =
             (p = 0.28)                 (p = 0.74)
                                                               0.28)
                                                             • Myocardial blush grade of 3: 76% vs. 59% (p
                                                               = 0.023), respectively
             50                 6
60
                           41           4.0                  • 6-month mortality: 4.0% vs. 3.1% (p = 0.74),
     %                              %                  3.1
30                              3                              respectively

0                               0
               ST-resolution
           ST-segment
                                         6-month mortality
                                         6-month
                                                             Conclusions
         resolution at 60                mortality           • Among STEMI patients, a strategy of
            minutes                                            aspiration thrombectomy compared with
                                                               primary PCI failed to improve ST-resolution
                                                               after PCI, although it did enhance myocardial
                                                               blush grade of 3
               Aspiration               Primary PCI
             thrombectomy                                    • Mortality was similar between the groups

                                                             Presented by Dr. Dariusz Dudek at ESC 2008
                                                   REGENT
        Trial design: Patients with acute MI and LV dysfunction (EF ≤40%) were randomized to
        selected CD34+ CXCR4+ bone marrow cells (n = 80), unselected bone marrow cells (n =
        80), or control (n = 40). Follow-up was 6 months.

                                                        Results
                    p = ns for stem cell LVEF
                     change compared with               • EF change: +3% selected cells (p = 0.04),
                             control                      +3% unselected cells (p = 0.01), 0% control (p
                                                          = 0.73) (p = ns between groups)
              20     335        3                  37
    3                                     21            • Death: 1.3%, vs. 1.3%, vs. 2.5% (p = 0.92),
                                                          respectively
%   2                                                   • Myocardial infarction: 5.0%, vs. 1.3%, vs.
                                                          5.0% (p = 0.61), respectively
    1

                                               0        Conclusions
    0
                                                        • In patients with acute MI and LV dysfunction,
                           Selected at
                   Change in LVEFcells6
                                                          both selected and unselected bone marrow
                        months
                                                          derived stem cells minimally increased LVEF
                                                          at 6 months
                             Unselected
             Selected        stem cells                 • This did not translate into a difference in LVEF
            stem cells                                    at follow-up between the groups
                              Control                   • Similar adverse events between the groups

                                                        Presented by Dr. Michal Tendera at ESC 2008
                                           REVERSE
    Trial design: Patients with LV dysfunction (NYHA class I-II) and wide QRS were
    randomized to cardiac resynchronization therapy (CRT) (n = 419) or optimal medical
    therapy (n = 191).

                                                  Results
                                                  • Patients worsened: 16% with CRT vs. 21% with
                         (p = 0.1)                  optimal medical therapy (p = 0.1)
                                                  • LV end-systolic volume index: decreased 18.4
    30                                              ml/m2 vs. 1.3 ml/m2 (p < 0.0001), respectively
                    16               21
%                                                 • Risk of heart failure hospitalization reduced with
    20
                                                    CRT (p = 0.03)

    10
                                                  Conclusions
     0
                                                  • CRT for mild heart failure does not reduce the
                     Percentage worsened
                  Percentage worsened               percentage of patients that clinically worsen
                                                  • CRT improves LV end-systolic volume index
                                                    and reduces the risk of hospitalization
              CRT                    Medical        compared with optimal medical therapy
                                     therapy



                                                   Presented Dr. Cecilia Linde at SCAI-ACC i2
                                                   Summit/ACC 2008
                                                  SEAS
  Trial design: Patients with asymptomatic mild to moderate calcific AS were randomized to
  treatment with ezetimibe/simvastatin 10/40 mg or placebo. Cardiovascular outcomes over 4
  years were compared.

                                                     Results
         (p = NS)                    (p = 0.05)      • 61% ↓ in LDL in ezetimibe/simvastatin arm
                                                     • No difference in the composite endpoint between
                 38.2       5                          the two groups (HR 0.96, 95% CI 0.83-1.12)
 40       35.3                       4.1
                            4                        • Increased incidence of cancer (9.9% vs. 7.0%, p =
 30                                                    0.03) and cancer deaths (4.1% vs. 2.5%, p = 0.05)
                                                       with ezetimibe/simvastatin
%                           3               2.5
                           %
 20
                            2                        Conclusions
 10                         1                        • No benefit with ezetimibe/simvastatin in
                                                       asymptomatic AS patients other than a reduction
                                                       in atherosclerotic events
 0                          0
      Composite endpoint        Deaths from cancer   • Final full publication is awaited

             Ezetimibe/             Placebo
             Simvastatin            (n = 930)
              (n = 943)
                                                     Pedersen TR. Press release July 21, 2008
                                                     SYNTAX
     Trial design: Patients with severe three-vessel disease or left main (LM) disease were
     randomized to either CABG or DES-PCI with paclitaxel-eluting stents. Clinical outcomes
     were compared at 12 months.

                                                          Results
                                                          • MACCE was significantly lower in CABG arm
         (p = 0.0015)                   (p = 0.0001)        compared with PCI (12.1% vs. 17.8%, p = 0.0015),
                                                            especially for diabetics (p = 0.0025)

                                 20                       • Significant ↓ in the need for repeat
    20           17.8                                       revascularization in CABG arm (p = 0.0001)

                                                 13.7     • Death and MI were similar; CVA ↑ with CABG (p =
    15                           15
          12.1                                              0.003)
%                            %
                                                          Conclusions
    10                           10
                                           5.9            • CABG was associated with fewer repeat
                                 5                          revascularizations compared with DES-PCI in
    5
                                                            patients with LM or three-vessel disease, but a
                                                            higher rate of stroke
    0                            0
                                                          • No difference in death, MI, or thrombosis
          MACCE                            Repeat
                                      revascularization   • Diabetics are especially more likely to benefit with
                  CABG                   DES-PCI
                                                            CABG compared with DES-PCI
                 (n = 897)               (n = 903)
                                                          Presented by Dr. Patrick Serruys at ESC 2008
                                SYNTAX Registry
   Trial design: Patients with severe three-vessel or left main (LM) disease who did not meet
   criteria for entry into the SYNTAX trial were followed for 12 months in the SYNTAX CABG
   and PCI registry.

                                                    Results
                                                    • Main reason for PCI only: inoperable (comorbidities);
                                                      main reason for CABG only: complex anatomy
                                                    • PCI outcomes: MACCE (20.4%), mortality (7.3%), MI
                                                      (4.2%), repeat revascularization (12%), CVA (0)
  25                       20
        20.4                                        • CABG outcomes: MACCE (8.8%), mortality (2.5%), MI
  20                                                  (2.5%), repeat revascularization (3%), CVA (2.2%)
                           15
% 15                   %
               12.0                                 Conclusions
                           10    8.8
  10
                                                    • The SYNTAX registry describes outcomes in PCI
  5                        5           3.0            and CABG in patients not eligible for the SYNTAX
                                                      trial
   0                       0                        • Of all-comers with three-vessel and/or LM disease,
        DES-PCI                   CABG                6.4% were considered inoperable; 35% not feasible
        (n = 198)               (n = 1,077)           for PCI
                                Repeat
               MACCE
                                revascularization
                                                     Presented by Dr. Friedrich Mohr at ESC 2008
                                          TIME-CHF
Trial design: Patients with chronic systolic HF were randomized to intensified BNP-guided
therapy or standard therapy, with the specific inclusion of patients ≥75 years. Clinical
outcomes were compared at 18 months.

                                                 Results
                                                • No difference in final NT-BNP between the 2 arms
                     (p < 0.05)
                                                • No difference in the survival (p = 0.06) or
           20                                     hospitalization-free survival (p = 0.46), but ↓ in CHF
                                                  hospitalization-free survival (p = 0.008)
           15                                   • Greater reductions in patients younger than 75 years
                                                • Quality of life better in older patients with standard
           10                                     therapy
       %             6.0
           5
                           2.0                   Conclusions

          0                                      • Intensified BNP-guided therapy was not associated
                                                   with better survival
         Change in quality of life,
             Age ≥75 years                       • Elderly patients do better with standard therapy,
                                                   including in quality-of-life assessment
         Standard                 Intensified
          therapy                   therapy
         (n = 248)                 (n = 251)

                                                 Presented by Dr. H.P. Brunner-La Rocca at ESC 2008
                                           TIMIC
Trial design: Patients with virus-negative inflammatory cardiomyopathy were randomized
to either immunosuppressive therapy with prednisone and azathioprine or placebo for 6
months. Echocardiographic parameters were compared at 6 months.

                                              Results

              (p < 0.05)                      • Majority in immunosuppressive therapy arm showed
                                                an ↑ in LVEF (26.4-48.0%) and ↓ in LV end-diastolic
                                                diameter (LVEDD) (68.6-52.8 mm)
                                              • None of the patients in the placebo arm improved;
 30           21.6                              some showed further ↓ in LVEF and ↑ in LVEDD

 15                                           Conclusions

% 0                                           • Immunosuppressive therapy in virus-negative
                                                inflammatory cardiomyopathy may be associated
                     -8.1                       with an improvement in LVEF and LVEDD,
 -15                                            compared with placebo

       Change in LVEF from baseline           • Clinical outcomes are awaited
                                              • May represent novel approach to heart failure
       Immunosuppressive                        management in these patients
            therapy             Placebo
            (n = 43)            (n = 42)
                                              Presented by Dr. Andrea Frustaci at ESC 2008
                                      TRANSCEND
     Trial design: Patients at high risk for cardiovascular events, and with intolerance to ACE
     inhibitors, were randomized to telmisartan or placebo. Patients were followed for a median
     of 56 months.

                                                     Results
         (p = 0.22)                (p = 0.49)        • No difference between telmisartan (15.7%) and
                                                       placebo (17.0%) in the incidence of the primary
                                                       outcome (CV death, MI, stroke, CHF) (p = 0.22)
20                          15                       • Stroke, death, or MI was reduced with telmisartan (p
             17.0                12.3 11.7             = 0.05)
      15.7
                                                     • No difference in mortality (p = 0.49); marginal
%                           10                         reduction in MI (3.9% vs. 5.0%, p = 0.06)
10                          %
                             5                       Conclusions
                                                     • Telmisartan is not more effective than placebo in
 0                           0                         reducing the incidence of the composite primary
                                                       endpoint, but does reduce the incidence of
      Primary endpoint              Mortality
                                                       stroke, death, or MI
             Telmisartan              Placebo        • May be an alternative in high-risk patients, who
              (n = 2,954)            (n = 2,972)
                                                       are intolerant to ACE inhibitors


                                                   TRANSCEND Investigators. Lancet 2008;Aug 31:[Epub]
        TCT 2008

Clinical Trial Summary Slides
                                        BBC ONE
  Trial design: Patients with bifurcation lesions were randomized to either a simple stepwise
  provisional T-stent strategy or a complex strategy involving either crush or culotte
  techniques. Clinical outcomes were compared at 9 months.


                                                  Results
       (p = 0.009)              (p > 0.05)
                                                  • MACE (death, MI, or TVF) was more frequent in
                                                    the complex strategy arm (HR 2.0, 95% CI 1.2-3.5,
                         20                         p = 0.009), as well as MI (p = 0.001)
 20
                                                  • Incidence of mortality, TVF, and stent thrombosis
        15.2                                        was similar between the two arms (p > 0.05)
 15                      15
                                                  • TIMI major bleeding was higher with the complex
%                    %                              strategy (1.2% vs. 0.4%, p > 0.05)
 10                      10
               8.0
                                                  Conclusions
 5                       5
                                 2.0              • A simple stepwise T-stent strategy is superior to a
                                       0.4          more complex strategy involving crush or culotte
 0                       0
                                                    techniques in patients with bifurcation lesions
         MACE                 Stent thrombosis

         Complex strategy       Simple strategy
            (n = 250)              (n = 250)
                                                  Presented by Dr. David J. Hildick-Smith at TCT 2008
                                             COOL RCN
     Trial design: Patients with pre-existing renal dysfunction undergoing cardiac
     catheterization were randomized to systemic hypothermia (core temperature 33-340C) or
     routine management. Clinical outcomes were compared at 30 days.


                                                       Results
           (p = 0.59)                 (p = 0.22)
                                                       • No difference in incidence of contrast-induced
                                                         nephropathy (CIN) between hypothermic and
100                          20                          normothermic groups (OR 1.27, 95% CI 0.53-3.00,
                                                         p = 0.59)
    80                                                 • No difference in serum creatinine at 24 hours
                             15                          (p = 0.30) and 48 hours (p = 0.09) post-procedure
    60                   %                             • All-cause mortality was similar (p = 0.22)
%                            10
    40
                                       5.2             Conclusions
           22.4              5
    20
                  18.6                       1.4       • Systemic hypothermia is not superior to routine
     0                       0                           hydration in patients with pre-existing renal
            CIN                        Mortality         dysfunction undergoing cardiac catheterization

          Hypothermia             Routine management
            (n = 63)                    (n = 73)
                                                       Presented by Dr. Gregg Stone at TCT 2008
                                       ENDEAVOR IV
  Trial design: ENDEAVOR IV was a randomized trial of the Endeavor zotarolimus-eluting
  stent (ZES) vs. the Taxus paclitaxel-eluting stent (PES) in patients undergoing PCI for
  single de novo coronary lesions. Clinical outcomes were compared at 2 years.


                                                      Results
        (p = 0.93)                    (p = 1.0)       • MACE was similar between the two arms (p = 0.93)
                                                      • Incidence of non-Q-wave MI was lower in the ZES
 20                           20                        arm (p = 0.022), whereas target vessel failure was
                                                        similar between the two arms (p = 0.23)

 15                           15                      • Overall rates of stent thrombosis similar (p = 1.0)

%             10.0        %
        9.8                                           Conclusions
 10                           10
                                                      • Among patients undergoing PCI for single de novo
 5                            5                         lesions, use of ZES was associated with a similar
                                                        incidence of MACE, target vessel failure, and stent
                                      1.1   0.9
 0                            0                         thrombosis compared with PES at 2 years
         MACE                      Stent thrombosis   • Lower rate of non-Q-wave MI noted with ZES
                                                        compared with PES needs to be corroborated by
                                        PES
                                                        other studies
                ZES
              (n = 773)               (n = 775)
                                                      Presented by Dr. Martin Leon at TCT 2008
                                             FAME
  Trial design: Patients with multivessel disease were randomized to either routine
  angiography-guided PCI or fractional flow reserve (FFR)-guided PCI, with stenting of only
  those lesions with an FFR of ≤0.8. Clinical outcomes were compared at 1 year.

                                                 Results
        (p = 0.02)             (p = 0.19)       • Resource utilization (contrast: 272 vs. 302 ml, cost
                                                  of procedure ($5,332 vs. $6,007) shorter with FFR-
                                                  guided PCI compared with routine PCI (all p < 0.05)
 20            18.4       20
                                                • MACE lower at 1 year with FFR (p = 0.02)
                                                • Incidence of death (p = 0.19), MI (p = 0.07), and
 15     13.2              15                      CABG or re-PCI (p = 0.08) at 1 year were similar
%                     %
 10                       10                     Conclusions

 5                        5                      • FFR-guided PCI is associated with a lower
                                      3.0          incidence of MACE compared with angiography-
                                1.8
                                                   guided PCI in patients with multivessel disease,
 0                         0
                                                   with a decrease in resource utilization
         MACE                     Death
                                                 • Further studies validating these findings are
                                                   necessary
          FFR-guided PCI       Routine PCI
             (n = 509)          (n = 496)
                                                 Presented by Dr. Nico Pijls at TCT 2008
                                    HORIZONS-AMI
     Trial design: STEMI patients undergoing primary PCI were randomized to bivalirudin (n =
     1,800) or heparin plus a glycoprotein (GP) IIb/IIIa inhibitor (n = 1,802). The investigator was
     not blinded to treatment assignment. Patients were followed for 30 days.

                                                      Results
                                                      • Unfractionated heparin was used prior to
            (p = 0.005)            (p < 0.001)          randomization in 66% of patients
                                                      • Death, MI, TVR, stroke, or bleeding: 9.2% for
                                                        bivalirudin vs. 12.1% for heparin + GP IIb/IIIa
15                                                      inhibitor (p = 0.005)
            9.2   12.1
                                                      • Major bleeding: 4.9% vs. 8.3% (p < 0.001),
                                   4.9      8.3
10                                                      respectively
%
 5                                                    Conclusions
                                                      • During primary PCI, bivalirudin alone is
 0                                                      superior to heparin plus a GP IIb/IIIa inhibitor
      Death, MI, TVR, stroke,
             MACE               Major bleeding
                                 major bleeding
                                                      • Bivalirudin alone reduces the composite of
           or bleeding
                                                        death, myocardial infarction, target vessel
                                                        revascularization, stroke, or bleeding
            Bivalirudin           Heparin +
                                  GP IIb/IIIa         • Improvement in the primary outcome was
               alone
                                  inhibitor             driven by a reduction in major bleeding

                                                      Stone GW, et al. N Engl J Med 2008;358:2218-30
                                    HORIZONS-AMI Stent
  Trial design: Patients presenting within 12 hours with a STEMI were randomized in a 3:1
  fashion to receive either paclitaxel-eluting (PES) or bare-metal stents (BMS). Clinical
  outcomes were compared at 9 months.


                                                         Results
          (p = 0.01)*                  (p = 0.72)
                                                        • Significant ↓ in ischemia-driven target lesion
                                                          revascularization (TLR) in the PES arm (4.5% vs.
                                                          7.5%, HR 0.59, 95% CI 0.43-0.83, p = 0.002)
 20                            20
                                                        • PES non-inferior to BMS in the incidence of MACE
                                                          (p for non-inferiority = 0.01)
 15                            15                       • Mortality (p = 0.98), stent thrombosis (p = 0.72), and
%                          %                              MI (p = 0.31) similar between the two arms;
 10                            10                         angiographic restenosis lower with PES (p <
           8.1     8.0                                    0.0001)

 5                             5        3.1    3.4       Conclusions
 0                             0                        • PES superior to BMS in reducing restenosis and
                                                          TLR at 1 year in patients with STEMI
            MACE                     Stent thrombosis
                PES                       SES           • Mortality, stent thrombosis, MACE rates similar
             (n = 2,257)                (n = 749)
 * For non-inferiority                                   Presented by Dr. Gregg Stone at TCT 2008
                                        ISAR-Left Main
  Trial design: Patients undergoing left main (LM) stenting were randomized to receive
  either paclitaxel-eluting (PES) or sirolimus-eluting stents (SES). Clinical outcomes were
  compared at 1 year.


                                                         Results
         (p < 0.001)*                 (p > 0.05)
                                                       • PES non-inferior to SES in the incidence of MACE
                                                         (RR 0.85, 95% CI 0.56-1.29; pnon-inferiority < 0.001)

 20                            20                      • Incidence of death, MI, stroke, and repeat
                                                         revascularization similar between the two arms (all
                  15.8                                   p > 0.05)
 15       13.6                 15                      • Stent thrombosis similar in both arms (0.3% vs.
%                          %                             1.0%, p > 0.05) at 2 years
 10                            10
                                                         Conclusions
 5                             5
                                                       • PES non-inferior to SES for the incidence of MACE
                                       0.3   1.0         at 1 year for unprotected LM stenting
 0                             0
                                                       • Rates of stent thrombosis similar up to 2 years of
            MACE                    Stent thrombosis     follow-up
                 PES                      SES
               (n = 302)                (n = 305)

 * For non-inferiority                                   Presented by Dr. Julinda Mehili at TCT 2008
                                               ISAR-TEST-2
      Trial design: Patients undergoing PCI were randomized in a 1:1:1 fashion to either dual
      DES (probucol + rapamycin), sirolimus-eluting (SES), or zotarolimus-eluting stents (ZES).
      Clinical outcomes were compared at 1 year.

                                                            Results
           (p = 0.003)                     (p = 0.87)       • Angiographic restenosis similar between dual-DES
                                                              (11.0%) and SES (12.0%) (p = 0.68), but higher
                                                              with ZES (19.3%) (p = 0.002) (p = 0.003 overall)
20                    19.3       20                         • Target lesion revascularization (TLR) similar
                                                              between dual-DES (6.8%) and SES (7.2%)
                                                              (p = 0.83), but higher with ZES (13.6%) (p = 0.001)
15                               15
                                                            • Incidence of MI (p = 0.8) and stent thrombosis
%         11.0 12.0          %                                (p = 0.87) similar between the three arms
 10                              10
                                                            Conclusions
 5                               5
                                                            • Dual-DES associated with a similar incidence of
                                           0.9 0.9 0.6        angiographic restenosis and TLR compared with
 0                               0                            SES, but lower than ZES
 Angiographic restenosis                 Stent thrombosis   • Incidence of MI and stent thrombosis similar at
         Dual-DES              SES               ZES          1 year
         (n = 333)           (n = 335)         (n = 339)
                                                            Presented by Dr. Robert Byrne at TCT 2008
                                                        ODESSA
      Trial design: ODESSA assessed the utility of optical coherence tomography (OCT) in
      evaluating strut coverage and malapposition of sirolimus-eluting (SES) vs. paclitaxel-eluting
      (PES) vs. zotarolimus-eluting (ZES) vs. bare-metal stents (BMS) in vivo.

                                                                     Results
           (p < 0.05)                          (p < 0.05)
                                                                     • Incidence of uncovered/malapposed struts was
                                                                       highest with SES, and lowest with ZES for both
                                 100                                   overlapping and non-overlapping stents (p < 0.05)
 20
                                                                     • % intimal hyperplasia was lowest with SES and
                                  80                                   highest with BMS (p < 0.05)
                                  60                         57.8    • Clinical outcomes at 6 months were similar
 %
10     8.7 8.3                   %                   45.2
                                  40          31.5                   Conclusions
                                       19.3
                        1.8       20                                 • Inverse relationship between incidence of
                 0.05                                                  uncovered/malapposed struts, and % intimal
  0                               0
                                                                       hyperplasia
Uncovered/malapposed        % intimal hyperplasia                    • OCT findings are interesting, but clinical
struts (overlapping stents)                                            significance and overall utility are unclear
        SES              PES             ZES                BMS
       n = 22           n = 22          n = 22              n = 11   Presented by Dr. Giulio Guagliumi at TCT 2008
                                           PREPARE
     Trial design: Patients presenting within 6 hours with a STEMI were randomized to either
     PCI with a Proxis (thrombus aspiration + embolic protection) device or routine PCI. Clinical
     outcomes were compared at 30 days.


                                                     Results
            (p = 0.009)             (p > 0.05)
                                                     • Incidence of >70% ST-resolution (STR) was higher
                                                       with the Proxis device in the immediate post-
                                                       procedure period (p = 0.009), but not thereafter
100                            20
                                                     • Post-PCI TIMI grade 3 flow (p = 0.06), myocardial
    80                                                 blush grade 3 (p = 0.93) were similar between the
             66.0              15                      two arms
    60                     %                         • MACE, mortality, MI, and stroke similar at 30 days
%                   50.0
                               10          7.0
    40                                               Conclusions
                               5    4.0
    20                                               • Proxis device was associated with a higher
                                                       incidence of >70% STR than routine PCI only in
     0                         0                       the post-PCI period
         >70% STR post-PCI            MACE           • No impact on TIMI grade 3 flow or clinical
                                                       outcomes
                Proxis + PCI          PCI alone
                  (n = 141)            (n = 143)
                                                     Presented by Dr. Karel Koch at TCT 2008
                                      SORT-OUT III
Trial design: SORT-OUT III was a randomized trial of the Endeavor zotarolimus-eluting
stent (ZES) vs. the sirolimus-eluting stent (SES) in patients undergoing PCI. Clinical
outcomes were compared at 9 months.


                                                 Results
                    (p = 0.02)                   • MI (p = 0.03), definite stent thrombosis (p = 0.02),
                                                   target lesion revascularization (p < 0.0001), and
         20                                        clinically significant restenosis (p < 0.0001) were all
                                                   more frequent with ZES compared with SES
         15                                      • Overall mortality was similar (p = 0.27)
     %
         10                                      Conclusions

         5                                       • ZES associated with worse outcomes, including
                                                   stent thrombosis, compared with SES at 9 months
                    1.2     0.2
         0                                       • Long-term follow-up data are awaited
                                                 • Similar to other trials showing higher restenosis
                Stent thrombosis                   with ZES; further investigation is required

                 ZES                  SES
              (n = 1,162)          (n = 1,171)
                                                 Presented by Dr. Jens Flensted Lassen at TCT 2008
                                                ZEST-AMI
      Trial design: Patients undergoing primary PCI for STEMI were randomized in a 1:1:1
      fashion to either zotarolimus-eluting (ZES), sirolimus-eluting (SES), or paclitaxel-eluting
      stents (PES). Clinical outcomes were compared at 1 year.


                                                           Results
            (p = 0.83)                   (p = 0.17)
                                                          • No difference in MACE (p = 0.83), ischemia-driven
                                                            TVR (p = 0.74), stent thrombosis (p = 0.17), MI (p =
20                             20                           0.11), or death (p = 0.14) between the three groups
                                                          • In-stent restenosis was lowest with SES (1.4%)
15                             15                           compared with ZES (15.9%) and PES (9.6%) at 8
                                                            months (p = 0.009)
%         11.1             %
 10              9.1 9.1       10
                                                           Conclusions
 5                             5             3.6
                                                   2.7    • No difference in clinical outcomes between ZES,
                                         0                  SES, and PES, but SES are associated with the
 0                             0                            lowest incidence of in-stent restenosis, when used
              MACE                     Stent thrombosis     in patients with STEMI

            ZES              SES               PES
          (n = 108)        (n = 110)         (n = 110)
                                                           Presented by Dr. Cheol-Hwan Lee at TCT 2008
        AHA 2008

Clinical Trial Summary Slides
                                          APPROACH
    Trial design: Diabetic patients were randomized to rosiglitazone titrated to 8 mg daily (n =
    333) vs. glipizide titrated to 15 mg daily (n = 339). IVUS was performed at baseline and 18
    months.

                                                    Results
                                                    • Change in percent atheroma volume: -0.21%
                      (p = 0.12)                      with rosiglitazone vs. 0.43% with glipizide (p =
                                                      0.12)

0.6                                                 • Change in total atheroma volume: -3.9 mm3 vs.
                                                      1.2 mm3 (p = 0.04), respectively
                              0.43
%                                                   • Death: 2.4% vs. 2.1%, respectively
0.3                                                 • Myocardial infarction: 2.1% vs. 1.8%,
                                                      respectively
                   -0.21
    0
                                                    Conclusions
                                                    • Among type 2 diabetic patients, the use of
                                                      rosiglitazone does not reduce percent atheroma
-0.3                                                  volume compared with glipizide
           Change in percent atheroma volume
                                                    • There was a reduction in total atheroma volume
                                                      with rosiglitazone
         Rosiglitazone             Glipizide
                                                    • CV outcomes were similar between groups

                                                     Presented by Dr. Richard Nesto at AHA 2008
                                     ATLAS TIMI 46
  Trial design: Patients with ACS were randomized to either rivaroxaban twice daily, once
  daily, or placebo. Clinical outcomes were compared at 6 months.


                                                    Results
                                                   • No difference between rivaroxaban and placebo in
         (p = 0.10)               (p = 0.028)
                                                     the primary outcome (death, MI, stroke, severe
                                                     ischemia) (HR 0.79, 95% CI 0.60-1.05, p = 0.10)
                            20                     • ↓ in death, MI, stroke with rivaroxaban (p = 0.028)
 20
                                                   • Dose-response curve for bleeding with rivaroxaban,
                                                     especially in the setting of dual antiplatelet therapy
 15                         15                       (p < 0.001)
%                       %
 10                         10
                7.0
          5.6                              5.5      Conclusions
 5                          5       3.9            • Rivaroxaban has reasonable efficacy compared with
                                                     placebo in patients with ACS, with a higher bleeding
 0                          0                        risk
      Primary outcome            Death/MI/Stroke   • ATLAS TIMI 46 was a phase II clinical trial
        Rivaroxaban                 Placebo          conducted to identify safe and effective doses of
         (n = 1,166)               (n = 1,160)       rivaroxaban to be used in the phase III trial

                                                    Presented by Dr. C. Michael Gibson at AHA 2008
                                        BACH
Trial design: BACH was a biomarker trial, which compared the prognostic accuracy of mid
regional pro-Adrenomedullin (MR-proADM), BNP, and NT-proBNP for 90-day mortality in
patients presenting to the emergency room with shortness of breath.

                                              Results

                (p < 0.001)                   • In the group admitted with CHF, MR-proADM
                                                was associated with a higher prognostic
                                                efficacy than both BNP and NT-proBNP (p <
      100
                                                0.001 for both)
               73.5                           • Log MR-proADM was associated with a
                      60.8 63.6                 significant improvement in prognostic ability
                                                for 90-day mortality in the multivariate model
    % 50                                        (p < 0.001)


                                              Conclusions
                                              • The diagnostic ability of MR-proADM for CHF
        0                                       is unclear
     Prognostic accuracy in CHF patients      • Clinical utility of these findings is limited

  MR-proADM           BNP         NT-proBNP


                                              Presented by Dr. Stefan Anker at AHA 2008
                                           BICC
Trial design: Patients with CVC were randomized to either high-dose (8 million IU), low-
dose (4 million IU) IFNB-1b, or placebo. Outcomes were compared at 24 weeks.


                                              Results
                  (p = 0.048)                 • Viral load reduction or elimination was better in
                                                IFNB-1b groups compared with placebo (p = 0.048)
      40
                                              • NYHA class was similar at 24 weeks (p = 0.073),
                      32                        quality of life was better in IFNB-1b group (p =
                                                0.032)
                                              • No change in echo or hemodynamic parameters
  % 20                     17                 • Serious adverse events were similar (p > 0.05)


                                              Conclusions

      0                                       • IFNB-1b was associated with a nearly twofold
                                                increase in viral load reduction or elimination
 Viral load reduction or elimination            compared with placebo in patients with CVC
          IFNB-1b               Placebo       • Results of phase III trial are awaited
           (n = 95)             (n = 48)


                                               Presented by Dr. Heinz Peter Schultheiss at AHA 2008
                                            FIT Heart
    Trial design: Family members of a hospitalized cardiac patient were randomized to a
    special intervention program for risk factor modification (n = 250) vs control (n = 251).
    Follow-up was 1 year.

                                                     Results
          Percent change in LDL cholesterol
                                                     • Percent change in LDL: -1.0% for special
-0.5                                                   intervention vs. -2.0% for control (p = NS)
                                                     • HDL at follow-up: 58.7 mg/dl vs. 57.6 mg/dl (p =
                                                       0.01), respectively
%




                   -1.0                              • BMI at follow-up: 27.7 kg/m2 vs. 28.4 kg/m2 (p =
                                                       0.88), respectively
-1.5
                                                     Conclusions
                                                     • Among family members of a hospitalized cardiac
                                -2.0                   patient, a special intervention program is not more
                                                       effective than a control program in lowering LDL
                                                       cholesterol
-2.5                      (p = NS)
                                                     • Special intervention was associated with a slightly
                                                       higher HDL, although similar BMI at follow-up
       Special intervention            Control
            program

                                                   Mosca L, et al. Circ Cardiovasc Qual Outcomes 2008;1:98-106
                                                      HF-ACTION
  Trial design: Patients with symptomatic systolic CHF on optimal medical therapy were
  randomized to either exercise training or usual medical care. Clinical outcomes were
  compared at 3 years.

                                                                Results
                                                                • No difference in mortality/hospitalizations between
          (p = 0.26)                          (p < 0.0001)
                                                                  the two arms (HR 0.93, 95% CI 0.84-1.02, p = 0.13).
                                                                  On adjustment for other prognostic factors, was ↓ in
                                                                  exercise training arm (p = 0.03)
 20                                  1.0
                                                                • CV mortality & CV hospitalizations (p = 0.14),
                                                                  6-minute walk distance (p = 0.26) similar, but peak
 15                                             0.7               VO2 higher in the exercise training arm
                 13
           12
m                                                               • Serious side effects similar between the two arms
                         ml/min/kg




 10                                  0.5
                                                                Conclusions
 5                                                              • Prescribed exercise training program in patients with
                                                      0.1         systolic CHF safe and effective, when added on to
 0                                    0                           optimal medical therapy
      Change in 6-minute                   Change in Peak VO2   • Strengthens current recommendations for exercise
        walk distance                                             in CHF patients
         Exercise training                     Usual care
            (n = 1,159)                        (n = 1,172)

                                                                Presented by Dr. David Whellan at AHA 2008
                                   HF-ACTION Substudy
         Trial design: Patients with CHF (NYHA II-IV) were randomized to an aerobic exercise
         training program (n = 1,159) vs. usual care (n = 1,172). Median follow-up was 2.5 years.


                                                        Results
                              (p = 0.001)
                                                        • Kansas City Cardiomyopathy Questionnaire
                                                          score at follow-up: +5 points in the exercise
     6                                                    group vs. +2 points in the usual care group (p =
                       5                                  0.001)
                                                        • Clinical improvement: 53% of the exercise group
                                                          vs. 33% of the usual care group (p < 0.001)
Points




     3
                                     2
                                                        Conclusions
                                                        • Among patients with CHF due to LV systolic
                                                          dysfunction, participation in an exercise program
     0                                                    modestly improves health status compared with
                          HF City
            Change in Kansas score Cardiomyopathy         usual care
                 Questionnaire at follow-up
                                                        • This benefit is seen early, within the first 3 months

             Exercise group              Usual care

                                                        Presented by Dr. Kathryn Flynn at AHA 2008
                                     I-PRESERVE
  Trial design: Patients with heart failure and preserved ejection fraction (EF) were
  randomized to either irbesartan or placebo. Clinical outcomes were compared at 5 years.



                                                Results
         (p = 0.35)              (p = 0.98)
                                               • No difference between irbesartan and placebo arms
                                                 in the primary outcome (death/CV hospitalization)
                                                 (HR 0.95, 95% CI 0.86-1.05, p = 0.35)
100                         20
                                               • Incidence of mortality (p = 0.98), worsening CHF (p
                                                 > 0.05), change in NT-proBNP (p = 0.14) similar
                            15                 • Most side effects similar, except ↑ risk of serious
%                       %        10.7 10.7       hyperkalemia with irbesartan (3% vs. 2%, p = 0.01)
 50                         10
         36.0 37.0
                                                Conclusions
                            5
                                               • Irbesartan was not associated with a reduction in
                                                 CV mortality and morbidity in patients with heart
 0                          0
                                                 failure and preserved EF
      Primary outcome             Mortality
                                               • Results were similar to those for candesartan and
         Irbesartan               Placebo        perindopril
         (n = 2,067)             (n = 2,061)

                                                Massie BM, et al. N Engl J Med 2008;Nov 11:[Epub]
                                                Presented by Dr. Peter Carson at AHA 2008
                                             JPAD
  Trial design: Patients with type 2 diabetes and no prior coronary artery disease were
  randomized in an open-label fashion to either aspirin 81 or 100 mg daily or no aspirin.
  Clinical outcomes were compared at 5 years.


                                                  Results
        (p = 0.16)             (p = 0.67)
                                                 • No difference between aspirin and nonaspirin group
                                                   in the total atherosclerotic events (HR 0.80, 95% CI
                                                   0.58-1.10, p = 0.16)
 20                       20
                                                 • Significant ↓ in fatal coronary and cerebrovascular
                                                   events (p = 0.0037)
 15                       15                     • No difference in nonfatal MI (p = 0.5), hemorrhagic
%                     %                            strokes (p = 0.48), mortality (p = 0.67)
 10                       10                     • ↑ bleeding with aspirin, not statistically significant
               6.7
         5.4                                      Conclusions
 5                        5
                                2.7    3.0       • Findings suggest no reduction in total
                                                   atherosclerotic events, but reduction in total
 0                        0
                                                   coronary and cerebrovascular events with aspirin in
  Atherosclerotic events        Mortality          diabetic patients
          Aspirin              No aspirin        • Findings need to be validated by other studies
        (n = 1,262)            (n = 1,277)

                                                  Ogawa H, et al. JAMA 2008;300:2134-41
                                                  Presented by Dr. Hisao Ogawa at AHA 2008
                                                                                           JUPITER
                          Trial design: Apparently healthy patients with LDL cholesterol <130 mg/dl and hs-CRP ≥2
                          mg/L were randomized to rosuvastatin 20 mg daily or placebo. Clinical outcomes were
                          compared at a median of 1.9 years.

                                                                                                    Results
                                                                                                    • Rosuvastatin associated with a significant ↓ in the
                               (p < 0.00001)                                      (p = 0.02)          primary outcome of MI, stroke, unstable angina,
                                                                                                      revascularization, or cardiovascular death (HR 0.56,
                                                                                                      95% CI 0.46-0.69, p < 0.00001)
                          2
Events/100 person-years




                                                Events/100 person-years



                                                                          2                         • All-cause mortality ↓ with rosuvastatin (p = 0.02)
                                                                                                    • Serious adverse effects were similar (p = 0.60)
                                        1.36
                                                                                         1.25
                                                                                   1.0
                          1                                               1                         Conclusions
                                 0.77
                                                                                                    • Rosuvastatin was associated with a significant
                                                                                                      reduction in major cardiovascular events, including
                                                                                                      death, in patients with LDL <130 mg/dl, but high hs-
                                                                                                      CRP (≥2.0 mg/L)
                          0                                               0
                                                                                                    • May require revision of current guidelines
                              Primary outcome                                 All-cause mortality
                                Rosuvastatin                                       Placebo
                                 (n = 8,901)                                      (n = 8,901)       Ridker PM, et al. NEJM 2008;359:2195-207

                                                                                                    Presented by Dr. Paul Ridker at AHA 2008
                                            PHS II
  Trial design: PHS II randomized healthy males in a factorial design to active vitamins E &
  C, active vitamin E & placebo vitamin C, placebo vitamin E & active vitamin C, & placebo
  vitamins E and C. Clinical outcomes were compared at 10 years.

                                                 Results
       (p = 0.86)               (p = 0.91)       • Neither vitamin C nor vitamin E associated with a
 20                     20                         reduction in major cardiovascular events compared
                                                   with placebo (p = 0.86, 0.91, respectively)
                                                 • No difference in individual outcomes studied
                        %                        • No increase in adverse events, except increased
%10     8.5    8.5                                 hemorrhagic stroke with vitamin E (p = 0.04)
                        10      8.4   8.6


                                                 Conclusions
 0                                               • Vitamins C or E not helpful in the primary
                         0
           Major cardiovascular events             prevention of cardiovascular events in healthy
                                                   patients
          Vit E                     Vit C
        n = 7,315                 n = 7,329      • Confirms earlier studies with vitamin E; one of the
                                                   first studies with vitamin C
         Placebo                  Placebo
         n = 7,326                n = 7,312
                                                 Sesso HD, et al. JAMA 2008;300:2123-33
                                                 Presented by Dr. J. Michael Gaziano at AHA 2008
                                          SEARCH
    Trial design: A 2 x 2 factorial study in which patients with a recent MI were randomized to
    either simvastatin 80 mg or 20 mg daily, and folic acid + vitamin B12 or placebo. Patients
    were followed for a mean of 6.7 years.

                                                     Results
                                                     • No difference in the incidence of major vascular
        (p > 0.05)                (p > 0.05)
                                                       events between high- vs. low-dose simvastatin, or
                                                       folate + vitamin B12 vs. placebo (p > 0.05 for both)
                                                     • No difference in individual outcomes studied
50
                            50                       • ↑ risk of myopathy in high-dose vs. low-dose
%                                                      simvastatin arms (0.88% vs. 0.05%, p < 0.05)
          24.5 25.7         %     25.5 24.8

0                           0
                                                     Conclusions
                 Major vascular events               • Neither high-dose (vs. low-dose) simvastatin nor
                                                       folate + vitamin B12 (vs. placebo) effective in
        Simvastatin 80 mg          Folate/ Vit B12
                                                       reducing major vascular events in patients with a
            n = 6,031                n = 6,033
                                                       recent MI

        Simvastatin 20 mg                            • Statin data contrary to other trials on this topic,
                                   Placebo
            n = 6,033              n = 6,031           folate + vitamin B12 data similar

                                                     Presented by Dr. Rory Collins at AHA 2008
                                                TIMACS
  Trial design: Patients with NSTEMI were randomized to an early (within 24 hours) or
  delayed (after 36 hours) invasive strategy. Clinical outcomes were compared at 6 months.


                                                        Results
                                                       • No difference in primary outcome (death, MI, stroke)
           (p = 0.15)                 (p = 0.81)
                                                         between the two arms (HR 0.85, 95% CI 0.68-1.06,
                                                         p = 0.15), except in high-risk patients (HR 0.65,
                                                         95% CI 0.48-0.88, p = 0.005)
 20                            20
                                                       • Death, MI, refractory ischemia ↓ in early invasive
                                                         arm (p = 0.0002), due to ↓ in refractory ischemia (p
 15                            15                        < 0.0001); death (p = 0.81), stroke (p = 0.74) similar

%                 11.4     %                           • Major bleeding was similar (p = 0.53)
            9.7
 10                            10
                                              6.0       Conclusions
                                       4.9
 5                             5                       • An early invasive strategy (within 24 hours) is not
                                                         associated with harm compared with a delayed
 0                             0                         invasive strategy (after 36 hours) in patients with
      Primary endpoint                  Mortality        NSTEMI, and may be beneficial in high-risk patients
                                                       • Significant reduction in refractory ischemia with an
          Early invasive            Delayed invasive
           (n = 1,593)                 (n = 1,438)
                                                         early invasive strategy

                                                        Presented by Dr. Shamir Mehta at AHA 2008
                                                                 THINRS
                     Trial design: Patients who required chronic anticoagulation were randomized to patient
                     self INR testing (n = 1,465) vs conventional monthly INR testing (n = 1,457). Follow-up was
                     4.5 years.

                                                                    Results
                                         (p = 0.1)
                                                                    • Death, stroke, or major bleeding: 7.9% per
                                                                      patient-year for self-testing vs. 8.9% per
                                                     8.9              patient-year for conventional testing (p = 0.1)
                     9
                                                                    • Death: 3.4% vs. 3.7%, respectively
% per patient-year




                                                                    • Major bleeding: 3.9% vs. 4.5%, respectively
                                      7.9
                     8

                                                                    Conclusions
                     7
                                                                    • Patient self-testing for INR monitoring does
                                                                      not reduce the composite outcome of death,
                                                                      stroke, or major bleeding
                     6          Death, stroke, or bleeding
                                 Death, stroke, or major major      • No signal for increased adverse events, such
                                          bleeding
                                                                      as major bleeding, with self-testing
                          Patient self               Conventional
                          INR testing                 INR testing

                                                                      Presented by Dr. Alan Jacobson at AHA 2008
                               VASP-Guided PCI
  Trial design: Patients undergoing nonemergent PCI, and a VASP index of ≥50% were
  randomized to either routine management, or VASP-guided further loading doses of
  clopidogrel until VASP index <50%. Clinical outcomes were compared at 30 days.

                                              Results
                                             • Stent thrombosis more frequent in the routine PCI
         (p = 0.03)            (p = 0.06)
                                               arm compared with VASP-guided PCI (p = 0.03)
                                             • MACE ↓ in the VASP-guided PCI arm (p < 0.001),
                          20                   mainly due to ↓ in MI (p = 0.01). Rates of
 20
                                               cardiovascular death, urgent revascularization were
                                               similar (p = 0.06 for both)
 15                       15                 • Bleeding rates were similar (p = 0.8)
%                     %
 10                       10
                                              Conclusions
                4.7                          • VASP-guided PCI, with an aim to reduce the VASP
 5                        5
                                      1.8      index below 50%, was associated with better
          0.5                    0             outcomes in patients undergoing nonemergent PCI
 0                        0
                                               and VASP index ≥50%
      Stent thrombosis          CV death
                                             • Needs to be corroborated by other studies
        VASP-guided PCI        Routine PCI
           (n = 214)            (n = 215)

                                              Presented by Dr. Frank Paganelli at AHA 2008

								
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